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  • Adner, MikaelKarolinska Institutet (författare)

Budesonide Prevents Cytokine-Induced Decrease of the Relaxant Responses to Formoterol and Terbutaline, but Not to Salmeterol, in Mouse Trachea

  • Artikel/kapitelEngelska2010

Förlag, utgivningsår, omfång ...

  • 2010-01-08
  • American Society for Pharmacology & Experimental Therapeutics (ASPET),2010

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:79f7151d-b810-46dc-a785-0818b8f0f8fb
  • https://lup.lub.lu.se/record/1587978URI
  • https://doi.org/10.1124/jpet.109.156224DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:120181753URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • During asthma exacerbations, increased airway inflammation may impair the effects of beta(2)-adrenoceptor (beta(2)AR) agonists. It is unclear whether this impairment is prevented by inhaled glucocorticoids (GCs). We have investigated the relaxation of carbachol-contracted mouse tracheal segments to the beta(2)AR agonists formoterol, terbutaline, and salmeterol. The segments were pre-exposed for 4 days to the proinflammatory cytokines tumor necrosis factor alpha (100 ng/ml) and interleukin-1 beta (10 ng/ml) with or without the GC, budesonide (1 mu M). Formoterol and terbutaline induced greater maximal relaxation (R-max)than salmeterol. The cytokines decreased R-max of all beta(2)AR agonists, whereas budesonide had no effect. However, after concomitant treatment with cytokines and budesonide, the R-max values of formoterol and terbutaline were not impaired, whereas budesonide did not prevent the decrease in the R-max of salmeterol. A similar pattern was observed for cAMP production by the agonists. In tracheal smooth muscle, beta(2)AR mRNA was not affected by the cytokines but increased with budesonide. However, the cytokines markedly increased cyclooxygenase (COX)-2 mRNA expression, which may lead to heterologous desensitization of beta(2)AR. It is noteworthy that the cytokine-induced increase of COX-2 was blocked by concomitant budesonide suggesting that heterologous desensitization of beta(2)AR by the cytokines may be prevented by budesonide treatment. Budesonide prevented cytokine-induced impairment of the tracheal relaxation and beta(2)AR/cAMP signaling for formoterol but not for salmeterol. This suggests that differences exist between formoterol and salmeterol in beta(2)AR coupling/activation and/or signal transduction upstream of cAMP. These results imply that maximal bronchodilator effects of formoterol, but not of salmeterol, are maintained by budesonide treatment during periods with increased inflammation, such as asthma exacerbations.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Larsson, BengtLund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kfar-bla (författare)
  • Safholm, JesperKarolinska Institutet (författare)
  • Naya, Ian (författare)
  • Miller-Larsson, Anna (författare)
  • Karolinska InstitutetAvdelningen för klinisk kemi och farmakologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Pharmacology and Experimental Therapeutics: American Society for Pharmacology & Experimental Therapeutics (ASPET)333:1, s. 273-2801521-01030022-3565

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